Infectious complications of car T‐cell therapy: A longitudinal risk model

Abstract

AbstractBackgroundCAR T‐cell therapy, where a patient's own T cells are re‐engineered to express a receptor to a target of interest, is becoming an increasingly utilized cancer‐directed therapy. There are significant toxicities that contribute to a novel state of immunocompromise, leading to new patterns of infectious complications that require further detailed study.MethodsWe created a single‐center cohort of adult recipients of CD19‐directed CAR T‐cell therapy and assessed infectious outcomes, supportive care received, toxicities, and markers of immune function up to 2 years following CAR T‐cell therapy. Descriptive statistics were used as appropriate for analysis. We additionally conducted time‐to‐event analysis assessing time‐to‐first infection with either log‐rank testing or Cox regression with univariate analysis, before including significant predictors into a multivariate Cox model of time to infection.ResultsWe identified 73 patients who received CD19‐directed CAR T‐cell therapy who predominantly had diffuse large B‐cell lymphoma. Within 30 days of cell infusion, bacterial and Candida infections were the most common, with 64% of infections due to these organisms. Between 30 days and 2 years postinfusion, respiratory viruses and pneumonia were the most frequent infections, with 68% of infections due to these etiologies. Receipt of tocilizumab, development of immune effector cell‐associated neurotoxicity syndrome (ICANS), or lower neutrophil count were associated with quicker onset of infection in a multivariate Cox model. imageConclusionsRespiratory viruses remain an important infectious complication of CAR T‐cell therapy following the first year. The model may be a useful tool to identify patients at the highest risk of infection.